Introduction to Basics of Pharmacology and Toxicology: Volume 2: Essentials of Systemic Pharmacology: From Principles to Practice

Foreword
Preface
Preface to Volume 1: General and Molecular Pharmacology: Principles of Drug Action (https://link.springer.com/book/10.1007/978...
Acknowledgments
Contents
Editors and Contributors
Part I: Autonomic Nervous System
1: Cholinoceptor Agonists and Anticholinesterase Agents
1.1 Introduction
1.2 Synthesis and Degradation of ACh
1.3 Cholinergic Receptors
1.4 Action of ACh in Different Organ Systems
1.4.1 Central Nervous System
1.4.2 Heart
1.4.3 Blood Vessels
1.4.4 Lungs
1.4.5 Gastrointestinal Tract
1.4.6 Urinary Tract
1.4.7 Eye
1.4.8 Glands
1.4.9 Skeletal Muscles
1.4.10 Ganglion
1.5 Cholinomimetic Drugs
1.5.1 Classification
1.5.2 Direct Muscarinic Agonists
1.5.3 Toxicology of Muscarinic Alkaloids
1.5.4 AChE and Anticholinesterases
1.5.5 Pharmacological Actions of Anticholinesterases
1.5.6 Therapeutic Uses of Anticholinesterases
1.6 Toxicology of Anticholinesterases: Management of OPC and Carbamate Poisoning
1.6.1 Acute Organophosphorus Poisoning
1.6.2 Acute Carbamate Poisoning
1.6.3 Intermediate Syndrome in OPC Poisoning
1.6.4 Delayed Neuropathy in OPC Poisoning
Bibliography
2: Cholinoceptor Antagonists
2.1 Introduction
2.2 Classification
2.3 Chemistry and Structure-Activity Relationship
2.4 Pharmacological Actions
2.4.1 Central Nervous System
2.4.2 Heart
2.4.3 Blood Vessels and Blood Pressure
2.4.4 Respiratory System
2.4.5 Eye
2.4.6 Gastrointestinal Tract
2.4.7 Urinary Bladder
2.4.8 Glands
2.4.9 Body Temperature
2.5 Individual Drugs
2.6 Therapeutic Uses
2.6.1 As Mydriatic and Cycloplegic
2.6.2 As Spasmolytics
2.6.3 Management of Overactive Bladder
2.6.4 As Pre-Anesthetic Medication
2.6.5 Bronchial Asthma and COPD
2.6.6 Motion Sickness
2.6.7 Arrhythmias
2.6.8 Drug-Induced Parkinsonism
2.6.9 In Poisoning
2.6.10 Other Uses with Unproven Efficacy
2.7 Adverse Effects and Contraindications
2.8 Management of Anticholinergic Poisoning
2.9 Ganglion Blockers
Bibliography
3: Adrenergic Agonists
3.1 Organ Specific Effects of Adrenergic Agonists
3.1.1 Cardiovascular System
3.1.1.1 Effect of the Alpha 1 Receptor Activation
Vascular Tone
Cardiac Parameters
Blood Pressure
3.1.1.2 Effect of Alpha 2 Receptor Activation
Peripheral Action
Central Action
3.1.1.3 Effect of Beta 1 Receptor Activation
Cardiac Parameters
3.1.1.4 Effect of Beta 2 Receptor Activation
3.1.1.5 Effect of Dopamine Receptor Activation
3.1.2 Effects on Other Organ Systems (Box 3.1)
Box 3.1 Effects on Other Organ Systems
3.2 Sympathomimetic Drugs
3.2.1 Endogenous Catecholamines
3.2.1.1 Epinephrine
Pharmacokinetics
Mechanisms of Action on Various Organ Systems and Uses of Epinephrine
Adverse Drug Reactions
Uses of Epinephrine
3.2.1.2 Norepinephrine
Cardiovascular System
Adverse Drug Reactions
Therapeutic Uses
3.2.1.3 Dopamine
Pharmacokinetics
Adverse Drug Reactions
Therapeutic Uses
Drugs Similar to Dopamine
3.2.2 Non-selective Beta Agonists
3.2.2.1 Isoproterenol
Therapeutic Uses
Adverse Drug Reactions
3.2.2.2 Dobutamine
Pharmacokinetics
Therapeutic Uses
Adverse Drug Reactions
3.2.3 Beta 2 Selective Receptor Agonists
3.2.3.1 Adverse Drug Reactions
Box 3.2 Drugs Used in the Pharmacotherapy of Asthma and COPD
3.2.3.2 Terbutaline
3.2.3.3 Ritodrine
3.2.4 Beta 3 Receptor Agonists
3.2.4.1 Mirabegron
3.2.5 Alpha 1 Agonists
3.2.5.1 Phenylephrine
3.2.5.2 Midodrine
3.2.6 Alpha 2 Agonists
3.2.6.1 Clonidine
Box 3.3 Miscellaneous Alpha 2 Agonists
3.2.7 Indirect Sympathomimetic Drugs
3.2.7.1 Amphetamine
Box 3.4 Amphetamine-Like Drugs
3.2.7.2 Cocaine
3.2.8 Mixed Acting Agents
3.2.8.1 Ephedrine
3.2.8.2 Metaraminol
Bibliography
4: Adrenergic Antagonists
4.1 Alpha Blockers
4.1.1 Effects of Alpha Receptor Blockade
4.1.1.1 Effects of Alpha 1 Blockade
4.1.1.2 Effects of Alpha 2 Blockade
4.1.2 Nonselective Alpha Antagonists
4.1.2.1 Treatment of Pheochromocytoma
4.1.2.2 Other Clinical Uses (Phentolamine)
4.1.2.3 Adverse Drug Reactions
4.2 Alpha 1 Selective Receptor Antagonists
4.2.1 Prazosin
4.2.1.1 Clinical Effects of Prazosin
4.2.1.2 Adverse Drug Reaction
4.2.1.3 Uses of Prazosin
4.2.2 Terazosin
4.2.3 Doxazosin
4.2.4 Tamsulosin
4.2.5 Silodosin
4.3 Alpha 2 Receptor Antagonists
4.3.1 Yohimbine
4.4 Beta Blockers
4.4.1 Effect on the Cardiovascular System
4.4.1.1 Heart
4.4.1.2 Conducting Tissue
4.4.1.3 Vasculature
4.4.2 Pulmonary System
4.4.3 Metabolic Effects
4.4.4 Special Properties of Various Beta Blockers
4.4.4.1 Nonselective Beta Blockers (First Generation)
4.4.4.2 Beta 1 Selective Blockers (Second Generation or Cardioselective Beta Blockers)
4.4.4.3 Beta Blockers with Additional Cardiovascular Effects (Third Generation Beta Blockers) (Box 4.1)
Box 4.1: Third Generation Beta Blockers
4.4.5 Common Uses of Beta Blockers
4.4.6 Adverse Effects of Beta Blockers (Box 4.2)
Box 4.2: Toxicity Profile of Beta Blockers
Bibliography
Part II: Central and Peripheral Nervous System
5: Neurotransmitters and Neurotransmission
5.1 Introduction
5.2 Relevant Anatomy
5.2.1 Cerebral Cortex
5.2.2 Diencephalon
5.2.3 Limbic System
5.2.4 Midbrain and Brainstem (Pons and Medulla)
5.2.5 Cerebellum
5.2.6 Spinal Cord
5.3 Neurochemical Transmission in the CNS
5.3.1 Neurotransmitters
5.3.2 Neuromodulators
5.3.3 Neuromediators (Second Messengers)
5.3.4 Neurohormones
5.3.5 Neurotrophic Factors
5.3.6 Co-transmission
5.4 Classification of Neurotransmitters
5.5 Receptors Involved in Neurotransmission
5.6 Amino Acids as Neurotransmitters
5.6.1 Gamma-Aminobutyric Acid (GABA)
5.6.2 Glycine
5.6.3 Glutamate
5.7 Amine Neurotransmitters
5.7.1 Acetylcholine
5.7.2 Dopamine
5.7.3 Norepinephrine
5.7.4 Epinephrine
5.7.5 Serotonin (5-hydroxytryptamine)
5.7.6 Histamine
5.8 Peptides as Neurotransmitters
5.9 Purines
5.10 Gaseous Neurotransmitters
5.10.1 Nitric Oxide
5.10.2 Carbon Monoxide
5.11 Lipid Mediators
Bibliography
6: Hypnotics and Sedatives
6.1 Introduction
6.1.1 History
6.2 Benzodiazepines
6.2.1 Introduction
Box 6.1: Classification of Benzodiazepines Based on Their Pharmacological Action
6.2.2 Mechanism of Action
6.2.2.1 Molecular Pharmacology of GABAA Receptor-Cl- Channel Complex
Box 6.2: Pharmacological Actions Mediated by Different Benzodiazepines Based on Subtype Binding of α Subunit of GABAA Receptor...
6.2.3 Pharmacological Actions
6.2.3.1 CNS Effects
6.2.3.2 Systemic Effects
6.2.4 Pharmacokinetics
Box 6.3: Routes of Administration of Benzodiazepines
Box 6.4: Benzodiazepines Categorized Based on Their Elimination Half-Lives
6.2.5 Drug Interactions
6.2.6 Adverse Effects
6.2.7 Therapeutic Uses (Table 6.3)
6.3 Barbiturates
6.3.1 Introduction
6.3.2 Mechanism of Action
6.3.3 Pharmacological Actions
6.3.4 Pharmacokinetics
Box 6.5: Routes of Administration of Various Barbiturates
6.3.5 Adverse Effects
6.3.6 Contraindications
6.3.7 Drug Interactions
6.3.8 Acute Barbiturate Poisoning
6.3.9 Therapeutic Uses
6.4 Non-Benzodiazepines or Non-Benzodiazepine Receptor Agonists (Non-BzRAs)
6.5 Benzodiazepine Antagonist: Flumazenil
6.5.1 Mechanism of Action
6.5.2 Pharmacokinetics
6.5.3 Adverse Effects
6.5.4 Uses
6.6 Newer Sedative-Hypnotics Acting Through Other Mechanisms
6.6.1 Melatonin Receptor Agonists
6.6.1.1 Ramelteon
6.6.1.2 Tasimelteon
6.6.2 Orexin Receptor Antagonists (Sleep-Enabling Drugs)
6.6.2.1 Dual Orexin Receptor Antagonists (DORAs)
6.6.2.2 Suvorexant
6.6.3 Tricyclic Antidepressant: Doxepin
6.7 Management of Insomnia
Box 6.6: Classification of Insomnia
Box 6.7: Management of Insomnia
6.8 Sedative-Hypnotics in the Evolving Stage
Box 6.8: Newer Drugs Under Trial for the Treatment of Insomnia
6.8.1 Molecular Targets for Newer Sedative-Hypnotics
Bibliography
7: Pharmacotherapy of Seizures
7.1 Introduction
7.2 Pharmacokinetics of Anti-Seizure Medications
7.3 Drug Interactions of Anti-Seizure Medications
7.4 Mechanism of Action of Anti-Seizure Medications
7.5 Classification of Anti-Seizure Medications
7.5.1 Drugs Acting Primarily on GABA
7.5.1.1 Barbiturates: Phenobarbitone, Primidone
7.5.1.2 Benzodiazepines: Diazepam, Clonazepam, Lorazepam, Clobazam, Clorazepate
7.5.1.3 Valproate
7.5.1.4 Gabapentin and Pregabalin
7.5.1.5 Tiagabine
7.5.1.6 Vigabatrin
7.5.1.7 Stiripentol
7.5.1.8 Ganaxolone
7.5.2 Sodium Channel Modulators
7.5.2.1 Phenytoin
7.5.2.2 Carbamazepine
7.5.2.3 Oxcarbazepine
7.5.2.4 Lamotrigine
7.5.2.5 Felbamate
7.5.2.6 Topiramate
7.5.2.7 Lacosamide
7.5.2.8 Rufinamide
7.5.3 Calcium Channel Modulators
7.5.3.1 Ethosuximide
7.5.3.2 Zonisamide
7.5.4 Drugs with Novel Mechanisms of Action
7.5.4.1 Levetiracetam
7.5.4.2 Perampanel
7.5.4.3 Lamotrigine
7.5.4.4 Acetazolamide
7.5.4.5 Phenobarbitone and Topiramate
7.6 Newer Drugs in Development
7.6.1 Brivaracetam
7.6.2 Eslicarbazepine Acetate
7.6.3 Retigabine (Ezogabine)
7.6.4 Carisbamate
7.7 Clinical Management of Epilepsy
7.8 Status Epilepticus
Bibliography
8: General Anesthetics
8.1 Evolution of Anesthetic Agents
8.2 Inhalational Anesthetic Agents
8.2.1 Classification: Based on Mechanism of Action
8.2.2 Pharmacokinetics of Inhalational Anesthetic Agents
8.2.2.1 General Considerations
8.2.2.2 Determinants of Partial Pressure Gradients
8.2.2.3 Solubility and Partition Coefficient
8.2.2.4 Tissue Blood Partition Coefficients
8.2.3 Pharmacodynamics of Inhaled Anesthetic Agents
8.2.3.1 Minimum Alveolar Concentration
8.2.3.2 Mechanism of Action of Inhalational Anesthetic Agents
8.2.4 Effect of Inhalational Anesthetic Agents on Organs
8.2.4.1 CNS
8.2.4.2 CVS
8.2.4.3 RS
8.2.4.4 Liver
8.2.4.5 Renal
8.2.4.6 Other Systems
8.2.5 Comparison of Inhalational Anesthetic Agents
8.3 Inducing (Parenteral) Anesthetic Agents
8.3.1 Introduction
8.3.2 Ideal Properties of Inducing Agents
8.3.3 Classification: Based on Mechanism of Action
8.3.4 Comparison of Inducing Agents Used in Anesthesia
8.4 Clinical Pharmacology of General Anesthetic Agents
8.4.1 Anesthesia in Liver Failure
8.4.2 Anesthesia in Renal Failure
8.4.3 Anesthesia in Seizure Disorders
8.4.4 Anesthesia in the Pediatric Population
8.4.5 Anesthesia in Pregnancy
Bibliography
9: Drug Therapy of Psychosis and Mania
9.1 Pharmacotherapy of Psychosis
9.1.1 Typical Antipsychotics
9.1.2 Atypical Antipsychotics
9.2 Pharmacotherapy of Mania (Mood Stabilizers)
9.2.1 Lithium as Mood Stabilizer
9.2.2 Antiepileptics as Mood Stabilizers
9.2.3 Antipsychotics as Mood Stabilizers
9.2.4 Other Adjuvants for Bipolar Disorder
Bibliography
10: Pharmacotherapy of Depression and Anxiety Disorders
10.1 Pharmacotherapy of Depression
10.1.1 Introduction
10.1.2 Drugs Used for Depression: Antidepressants
10.1.3 Common Mechanistic Pathways for Antidepressants
10.1.4 Classification of Antidepressants
10.1.4.1 Tricyclic Antidepressants (TCAs)
10.1.4.2 Selective Serotonin Reuptake Inhibitors (SSRIs)
10.1.4.3 Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
10.1.4.4 Atypical Antidepressants
10.1.4.5 Monoamine Oxidase Inhibitors (MAOIs)
10.1.5 Clinical Uses of Antidepressants (Other than in Depressive Disorders)
Box 10.1 Alternative Uses of Antidepressants
10.1.6 Advances in Antidepressant Therapy
10.2 Pharmacotherapy of Anxiety Disorders
10.2.1 Drugs for Treatment of Anxiety Disorders (Anti-Anxiety Drugs)
10.2.1.1 Antidepressants as Anti-Anxiety Drugs
10.2.1.2 Benzodiazepines
Box 10.2 BZDs Used in Anti-Anxiety Therapy
10.2.1.3 Anticonvulsants
10.2.1.4 Beta Blockers
10.2.1.5 Azapirones
10.2.1.6 Sedative Antihistaminics
10.2.2 Advances in Anti-Anxiety Drugs
Bibliography
11: Pharmacotherapy of Neurodegenerative Disorders
11.1 Parkinson´s Disease
11.1.1 Function of Basal Ganglia
11.1.2 Causes of PD
11.1.3 Symptoms of PD Include
11.1.4 Treatment of PD
11.1.4.1 Levodopa (L-DOPA, L-Dihydroxyphenylalanine)
11.1.4.2 Dopamine Receptor Agonists (Ropinirole and Pramipexole)
11.1.4.3 Catechol-O-Methyltransferase (COMT) Inhibitors
11.1.4.4 Selective MAO-B Inhibitors
11.1.4.5 Anti-cholinergic Agents
11.1.4.6 Newer Drugs
11.2 Alzheimer´s Disease (AD)
11.3 Amyotrophic Lateral Sclerosis (ALS)
Bibliography
12: Opioid Agonists and Antagonists
12.1 Definitions
12.2 Endogenous Opioid Peptides
12.3 Opioid Receptors
12.4 Effects of Clinically Used Opioids (Table 12.1)
12.5 Classification of Opioids (Box 12.1 and 12.2)
Box 12.1 Opioid classification based on synthetic process
Box 12.2 Opioid classification based on chemical structure/activity
12.6 Opioid Agonists
12.6.1 Morphine and its Congeners
12.6.1.1 Morphine
12.6.1.2 Codeine
12.6.1.3 Heroin
12.6.1.4 Hydromorphone
12.6.1.5 Oxycodone
12.6.1.6 Hydrocodone
12.6.1.7 Oxymorphone
12.6.1.8 Levorphanol
12.6.2 Piperidine Analgesics
12.6.2.1 Meperidine
12.6.2.2 Diphenoxylate
12.6.2.3 Loperamide
12.6.3 Fentanyl and its Congeners (Phenylpiperidine Analgesics)
12.6.3.1 Fentanyl and Sufentanil
12.6.3.2 Remifentanil
12.6.4 Other Opioid Agonists
12.6.4.1 Methadone
12.6.4.2 Tramadol
12.6.4.3 Tapentadol
12.6.4.4 Dextromethorphan
12.6.4.5 Pholcodine and Benzonatate
12.7 Opioid Partial Agonists
12.7.1 Pentazocine
12.7.2 Nalbuphine
12.7.3 Butorphanol
12.7.4 Buprenorphine
12.8 Opioid Antagonists
12.8.1 Pharmacological Properties
12.8.2 Effects in the Absence of Opioid Agonist
12.8.3 Effects in the Presence of Opioid Agonists
12.8.4 Effects in Opioid Dependent Patients
12.8.5 ADME
12.8.6 Therapeutic Uses
12.8.6.1 Treatment of Opioid Overdoses
12.8.6.2 Managing Constipation
12.8.6.3 Management of Abuse Syndromes
12.9 Routes of Analgesic Drug Administration
12.9.1 Patient Controlled Analgesia
12.9.2 Spinal Delivery
12.9.3 Rectal Administration
12.9.4 Transmucosal (Oral) Administration
12.9.5 Transnasal Administration
12.9.6 Transdermal Administration
12.10 Guidelines for Opiate Dosing
12.11 Factors Affecting Opioid Variability
12.12 Nonanalgesic Uses of Opioids
12.12.1 Dyspnoea
12.12.2 Anaesthetic Adjuvants
12.13 Acute Opioid Toxicity
12.13.1 Symptoms and Diagnosis
12.13.2 Treatment
Bibliography
13: Cognition Enhancers, Psychostimulants, and Psychedelic Drugs
13.1 Introduction
Box 13.1 List of Drugs Which Act as Cognition Enhancers, Psychostimulants, and Psychedelics
13.2 Cognition Enhancers
13.2.1 Cholinergic Activators
13.2.1.1 Tacrine
13.2.1.2 Rivastigmine
13.2.1.3 Donepezil
13.2.1.4 Galantamine
13.2.2 NMDA Antagonist
13.2.3 Miscellaneous
13.2.3.1 Piracetam
13.2.3.2 Pyritinol
13.2.3.3 Dihydroergotoxine
13.2.3.4 Citicoline
13.2.3.5 Ginkgo biloba
13.3 Psychostimulants
13.3.1 Methylxanthines
13.3.2 Reuptake Inhibitors
13.3.2.1 Cocaine
13.3.2.2 Amphetamine
13.3.2.3 Methylphenidate
13.3.2.4 Modafinil
13.3.2.5 Atomoxetine
13.4 Psychedelic Drugs
13.4.1 Indole Amines
13.4.1.1 Lysergic Acid Diethylamide (LSD)
13.4.1.2 Psilocybin
13.4.2 Phenylalkyl Amine
13.4.2.1 Methylenedioxymethamphetamine (MDMA, `Ecstasy´)
13.4.3 Arylcyclohexyl Amine
13.4.3.1 Phencyclidine
13.4.4 Cannabinoids
13.4.4.1 Marijuana
13.4.4.2 Synthetic Cannabinoids
Bibliography
14: Drug Dependence and Abuse
14.1 Ethanol
14.1.1 Acute Intoxication
14.1.2 Long-Term Complications
14.1.3 Treatment of Alcohol Dependence
14.2 Nicotine
14.2.1 Pharmacology
14.2.2 Treatment
14.3 Cannabinoids
14.3.1 Symptoms of Cannabis Abuse
Bibliography
15: Local Anesthetics
15.1 Introduction and Historical Overview
15.2 Chemical Properties of Local Anesthetics
15.3 Clinical Classification of Local Anesthetics
15.4 Mechanism of Action of Local Anesthetics
15.5 Pharmacological Actions of Local Anesthetics
15.5.1 Local Actions
15.5.2 Systemic Actions
15.5.2.1 CNS Effects
15.5.2.2 CVS Effects
15.6 Pharmacokinetics of Local Anesthetics
15.7 Adverse Effects of Local Anesthetics
15.8 Drug Interactions
15.9 Techniques of Local Anesthesia (Box 15.1)
Box 15.1 Overview of Local Anesthesia Techniques
15.10 Key Features of Individual Local Anesthetic Agents
15.10.1 Cocaine
15.10.2 Lignocaine
15.10.3 Bupivacaine
15.10.4 Other Agents
15.11 Recent Advances in Local Anesthesia
Bibliography
16: Skeletal Muscle Relaxants
16.1 Introduction
16.2 Peripherally Acting Muscle Relaxants
16.2.1 Non-Depolarizing Blockers
16.2.2 Depolarizing Blockers
16.2.3 Monitoring the Depth of Neuromuscular Block
16.3 Centrally Acting Muscle Relaxants
16.3.1 Mephenesin Group
16.3.2 Benzodiazepines
16.3.3 GABA Derivative
16.3.4 Central Alpha 2 Agonist
16.3.5 Other Centrally Acting Muscle Relaxants
16.4 Directly Acting Muscle Relaxants
16.5 Miscellaneous
16.5.1 Botulinum Toxin Type A and B
16.5.2 Other Drugs
Bibliography
Part III: Autacoids and Other Chemical Mediators
17: Histamine, Serotonin, Bradykinin, and the Ergot Alkaloids
17.1 Histamine
17.1.1 Structure and Chemistry
17.1.2 Biosynthesis and Catabolism
17.1.3 Distribution, Release, and Receptors
17.1.4 Physiopathological and Pharmacological Effects
17.1.4.1 Cardiovascular System
17.1.4.2 Nervous System
17.1.4.3 Gastrointestinal System
17.1.4.4 Bronchiolar Smooth Muscle
17.1.5 Antihistamines
17.2 Serotonin
17.2.1 Structure and Chemistry
17.2.2 Biosynthesis, Release, and Catabolism
17.2.3 Distribution and Receptors
17.2.4 Physiopathological and Pharmacological Effects
17.2.4.1 Central Nervous System
17.2.4.2 Cardiovascular System
17.2.4.3 Gastrointestinal System
17.2.4.4 Miscellaneous Effects
Serotonin Syndrome
17.2.5 Migraine Pharmacotherapy
17.2.5.1 Migraine Pathophysiology
17.2.5.2 Migraine Therapy
Triptans
Ditans
Gepants
Ergot Alkaloids
Nonsteroidal Anti-Inflammatory Drugs
Antiemetics
Migraine Prophylaxis
β-Adrenergic Blockers
Anticonvulsants
Antidepressants
Calcium Channel Blockers
Methysergide
Anti-CGRP Monoclonal Antibodies
17.3 Bradykinin
17.3.1 Structure and Chemistry
17.3.2 Biosynthesis and Metabolism
17.3.3 Receptors
17.3.4 Physiopathological Effects
17.3.4.1 Cardiovascular System
17.3.4.2 Pain and Inflammation
17.3.4.3 Respiratory System
17.3.4.4 Renal System
17.3.5 Therapeutic Applications
17.4 Ergot Alkaloids
17.4.1 Therapeutic Effects
17.4.2 Adverse Effects
Bibliography
18: Prostaglandins, Leukotrienes, and Related Compounds
18.1 Prostaglandins
18.1.1 History
18.1.2 Chemistry of Prostaglandins
18.1.3 Biosynthesis of Prostaglandins
18.1.4 Metabolism of Prostaglandins and Thromboxanes
18.1.5 Prostaglandin Receptors and Their Physiological Actions
18.1.6 Prostaglandin Analogs
18.2 Leukotrienes
18.2.1 Biosynthesis of Leukotrienes
18.2.2 Metabolism of Leukotrienes
18.2.3 Leukotriene Receptors and Its Physiological Action
18.2.4 Inhibitors of Leukotrienes
18.3 Platelet-Activating Factor (PAF)
18.4 Levuglandins (LGs)
18.5 Prostamides (PMs)
18.6 Esterified Eicosanoids
Bibliography
19: Non-Steroidal Anti-Inflammatory Medicines
19.1 Introduction
19.2 Mechanism of Action
19.3 Classification
19.3.1 Chemical Classification
19.3.2 Clinical Classification
19.4 Comparison of NSAIMs Based on Clinical Classification
19.5 Clinical Pharmacology of NSAIMs
19.5.1 NSAIMs in the Geriatric Population
19.5.2 NSAIMs in Pediatrics Population
19.5.3 NSAIMs During Pregnancy
19.5.4 NSAIMs in Liver Disease
19.5.5 NSAIMs in Renal Disease
19.5.6 NSAIMs in Cardiac Patients
Bibliography
20: Drug Used in Rheumatoid Arthritis
20.1 Pathophysiology
20.2 Management
20.2.1 Non-Steroidal Anti-Inflammatory Medicines (NSAIMs)
20.2.2 Corticosteroids
20.2.3 Methotrexate (MTX)
20.2.3.1 Side-Effects
20.2.4 Sulfasalazine (SSZ)
20.2.4.1 Side-Effects
20.2.5 Chloroquine and Hydroxychloroquine (HCQ)
20.2.5.1 Mechanisms
20.2.5.2 Side-Effects
20.2.6 Leflunomide (LEF)
20.2.7 Gold Salts
20.2.8 Immunosuppressants: Cyclosporine, Azathioprine
20.2.9 Tumor Necrosis Factor-Alpha (TNFα) Inhibitors
20.2.9.1 Side-Effects
20.2.10 Non-TNF Alpha Inhibitor Biologics
20.2.11 Tofacitinib
20.2.11.1 Side-Effects
20.3 Key Points on Usage of DMARDs
Bibliography
21: Pharmacotherapy of Gout
21.1 Introduction
21.2 Aetiology and Risk Factors
21.3 Pathophysiology of Gout
21.4 Clinical Features of Gout
21.4.1 Asymptomatic Stage
21.4.2 Acute Gout
21.4.3 Inter-Critical Stage
21.4.4 Chronic Gout
21.5 Investigation and Diagnosis
21.5.1 Laboratory Investigations
21.5.2 Diagnostic Criteria
21.6 Drugs Used in the Treatment of Gout
21.6.1 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
21.6.2 Colchicine
21.6.3 Corticosteroids
21.6.4 Urate Lowering Agents
21.6.4.1 Allopurinol
21.6.4.2 Febuxostat
21.6.4.3 Probenecid
21.6.4.4 Sulfinpyrazone and Benzbromarone
21.6.4.5 Lesinurad
21.6.5 Uricase
21.6.5.1 Pegloticase
21.6.5.2 Rasburicase
21.7 Management of Gout
21.7.1 Non-Pharmacological Treatment
21.7.2 Pharmacological Treatment
21.7.2.1 Asymptomatic Hyperuricaemia
21.7.2.2 Treatment of Acute Gouty Attack
21.7.2.3 Prophylaxis for Prevention of Acute Flares
21.7.2.4 Urate Lowering Therapy (ULT)
21.8 Drugs in the Pipeline
21.8.1 Interleukin-1 Antagonist
21.8.2 Arhalofenate
21.8.3 Verinurad
21.8.4 Pegsiticase
21.8.5 Tranilast
21.8.6 Levotofisospam
21.8.7 Ulodesine
Bibliography
22: Nitric Oxide, Vasoactive Peptides, and Purines
22.1 Nitric Oxide: Introduction
Box 22.1 Overview of agents related to Nitric oxide (NO)
22.2 Functions of NO
22.2.1 Smooth Muscle
22.2.2 Cell Adhesion
22.2.3 Inflammation
22.2.4 Others
22.3 NO Synthase (NOS)
22.4 NO Donors
22.5 Vasoactive Peptides: Introduction
22.6 Peptide Antagonists
22.7 Peptide Receptors
22.8 Peptides with Their Vasoactive Properties
22.8.1 Angiotensins
22.8.2 Cholecystokinin (CCK)
22.8.3 Vasoactive Intestinal Peptide (VIP)
22.8.4 Somatostatin
22.8.5 Substance P
22.8.6 Neurotensin (NT)
22.8.7 Opioid Peptides
22.8.8 Oxytocin (OT)
22.8.9 Parathyroid Hormone (PTH)
22.8.10 Prolactin
22.8.11 Thyrotropin-Releasing Hormone (TRH)
22.8.12 Urotensin I
22.8.13 Vasopressin
22.9 Purines: Introduction
22.10 Importance of Purines
22.11 Purine Catabolism
22.12 Biological Activities of Purine Analogues
22.12.1 Anti-Leishmanial Activity
22.12.2 Antiviral Activity
22.12.3 Antifungal Activity
22.12.4 Antibacterial Activity
22.12.5 Antitumor Activity
22.12.6 Antiprotozoal Activity
Bibliography
Part IV: Cardiovascular and Renal Pharmacology
23: Drugs Affecting Renal Excretory Function
23.1 Carbonic Anhydrase Inhibitors
23.1.1 Mechanism of Action
23.1.2 Clinical Effects
23.1.3 Therapeutic Uses
23.1.4 Adverse Drug Reactions
23.2 Osmotic Diuretics
23.2.1 Mechanism of Action
23.2.2 Therapeutic Uses
23.2.3 Adverse Drug Reactions
23.3 Na+-K+-2Cl- Symport Inhibitors
23.3.1 Mechanism of Action
23.3.2 Clinical Effects of Loop Diuretics
23.3.3 High-Ceiling Diuretics
23.3.4 Relevant Pharmacokinetics
23.3.5 Special Properties of Torsemide that Are Beneficial Clinically
23.3.6 Therapeutic Uses
23.3.7 Adverse Drug Reactions
23.3.8 Drug Interactions (Box 23.1)
Box 23.1 Drug Interactions of Loop Diuretics
23.4 Na+-Cl- Symporter Inhibitors
23.4.1 Mechanism of Action
23.4.2 Clinical Effects of Thiazide Diuretics
23.4.3 Differences Between Hydrochlorothiazide, Chlorthalidone and Indapamide
23.4.4 Therapeutic Uses
23.4.5 Adverse Drug Reactions
23.5 Renal Epithelial Na+ Channel Inhibitors
23.5.1 Mechanism of Action
23.5.2 Clinical Effects of ENaC Inhibitors
23.5.3 Therapeutic Uses
23.5.4 Adverse Drug Reactions
23.6 Aldosterone Antagonists
23.6.1 Mechanism of Action
23.6.2 Clinical Effects
23.6.3 Relevant Pharmacokinetics
23.6.4 Therapeutic Uses
23.6.5 Adverse Drug Reactions
23.7 Natriuretic Peptides
23.7.1 Mechanism of Action
23.7.2 Clinical Effects of Nesiritide
23.8 Adenosine Receptor Antagonists
23.9 Vasopressin Receptor Agonists
23.9.1 Therapeutic Uses of Vasopressin
23.9.2 Adverse Drug Reaction to Vasopressin
23.9.3 Use of Nitroglycerin with Vasopressin
23.9.4 Uses of Desmopressin
23.9.5 Adverse Drug Reactions to Desmopressin
23.9.6 Drugs Affecting Vasopressin Response in the Kidneys
23.10 Vasopressin Antagonists
23.11 Clinical Pharmacology of Diuretic Use
23.11.1 Diuretic Braking
23.11.2 Use in Chronic Renal Disease
23.11.3 Treatment of Oedema
23.11.4 Diuretics in Acute Renal Failure
Bibliography
24: Antihypertensive Agents
24.1 Introduction
24.2 ACE Inhibitors (ACEIs)
24.3 Angiotensin-II Type 1-Receptor b\Blockers (ARBs)
24.4 Calcium Channel Blockers (CCBs)
24.5 Diuretics
24.6 Beta-Blockers
24.7 Less Commonly Used Antihypertensive Agents
24.7.1 Alpha-1 Adrenergic Blockers
24.7.2 Centrally Acting Sympatholytic Drugs
24.7.3 Direct Vasodilators
24.7.4 Direct Renin Inhibitors
24.8 Antihypertensive Agents of Choice in the Different Subpopulation
24.9 Management of Hypertensive Emergencies
Bibliography
25: Treatment of Ischemic Heart Disease
25.1 Introduction
25.2 Pathophysiology of IHD
Box 25.1 Factors Associated with Myocardial Imbalance
25.3 Clinical Features of IHD
25.4 Principles of IHD Treatment
25.5 Treatment Strategies for IHD
25.5.1 Organic Nitrates
25.5.2 Beta-Adrenoceptor Antagonists (beta-Blockers)
25.5.3 Calcium Channel Blockers
25.5.4 Potassium Channel Openers
25.5.5 Specific Sinus Node Inhibitors
25.5.6 Late Sodium Current Inhibitors
25.6 Surgical Therapy for IHD
Bibliography
26: Drugs Used in Heart Failure
26.1 Pathophysiology
26.2 Treatment of Congestive Heart Failure
26.2.1 Diuretics
26.2.1.1 Loop Diuretics (Furosemide, Torsemide, Ethacrynic Acid, Bumetanide)
26.2.1.2 Thiazides (Hydrochlorothiazide, Chlorthalidone, Indapamide)
26.2.1.3 Potassium Sparing Diuretics
26.2.1.4 Diuretic Resistance
26.2.2 Angiotensin Converting Enzyme Inhibitors (ACEIs)
26.2.3 Beta-Blockers
26.2.4 Digoxin
26.2.5 Nitrates
26.2.6 Atrial Natriuretic Peptide and Vasopeptidase Inhibitors
Box 26.1 Mortality Reducing Drugs in CHF
26.3 Treatment of Severe Decompensated and Acute Heart Failure
Bibliography
27: Drugs Used in Cardiac Arrhythmias
27.1 Introduction
27.2 Electrophysiology of the Heart
27.2.1 The Ventricular Action Potential
27.2.2 The Electrocardiogram
27.3 Pathophysiology of Cardiac Arrhythmias
27.3.1 Abnormality in Impulse Formation
27.3.2 Abnormality in Impulse Conduction
27.4 Pharmacology of the Antiarrhythmic Drugs
27.4.1 Classification of Antiarrhythmic Drugs
27.4.2 Specific Antiarrhythmic Drugs
27.5 Therapeutic Use of Antiarrhythmic Drugs
27.5.1 Guiding Principles for Antiarrhythmic Drug Use
27.5.2 Non-Pharmacological Therapies
27.6 Conclusion
Bibliography
28: Pharmacotherapy of Shock and Drugs Used in Cardiopulmonary Resuscitation
28.1 Pharmacotherapy of Shock
28.1.1 Types of Shock
Box 28.1 Major Types and Related Causes of Shock
28.1.2 Principles of Shock Management
28.1.3 Fluid Management in Shock
28.1.3.1 Crystalloid Fluids/Plasma Substitutes
28.1.3.2 Colloidal Fluids/Plasma Substitutes
Box 28.2 Similarities and Differences Among the Colloidal Plasma Substitutes
28.1.3.3 Whole Blood, Blood Products, and Plasma
28.1.4 Inotropes in Shock
28.1.5 Type-Specific Management of Shock
Box 28.3 Management Protocols for Different Types of Shock
28.2 Drugs Used in Cardiopulmonary Resuscitation
Bibliography
29: Pharmacotherapy of Pulmonary Arterial Hypertension
29.1 Introduction
29.2 Endothelin-1 Receptor Antagonists
29.3 Drugs Targeting Nitric Oxide Pathway
29.3.1 Phosphodiesterase-5 Inhibitors
29.3.2 Soluble Guanylate Cyclase Stimulators
29.4 Drugs Targeting Prostacyclin Pathway
29.5 Approach to a Patient with PAH
Bibliography
30: Antiplatelets, Anticoagulants, and Fibrinolytics
30.1 Hemostasis
30.1.1 Primary Hemostasis
30.1.2 Secondary Hemostasis
30.1.3 Fibrinolysis
30.2 Antiplatelet Drugs
30.2.1 Aspirin
30.2.2 Clopidogrel
30.2.3 Prasugrel
30.2.4 Ticagrelor and Cangrelor
30.2.5 Abciximab, Eptifibatide, and Tirofiban
30.2.6 Vorapaxar
30.2.7 Dipyridamole and Cilostazol
30.2.8 Adverse Effects, Complications, and Contraindications of Antiplatelet Drugs
30.3 Anticoagulants
30.3.1 Heparin and Other Indirect Thrombin Inhibitors
30.3.2 Warfarin and Other Vitamin K Antagonists
30.3.3 Direct Thrombin Inhibitors
30.3.4 Adverse Effects, Complications, and Contraindications of Anticoagulant Drugs
30.4 Fibrinolytics
30.4.1 Recombinant T-PA and Its Variants
30.4.2 Adverse Effects, Complications, and Contraindications of Fibrinolytic Drugs
30.5 Conclusion
Bibliography
31: Drugs Used inDyslipidemia
31.1 Introduction
31.2 Biochemistry of Lipoproteins
31.3 Statins
31.3.1 Mechanism of Action
31.3.2 Effects on Lipids
31.3.3 Pleiotropic Effects of Statins
31.3.4 Adverse Effects
31.3.5 Drug Interaction
31.3.6 Clinical Use
31.4 Fibrates
31.4.1 Mechanism of Action
31.4.2 Effect on Lipids
31.4.3 Other Effects of Fibrates
31.4.4 Adverse Effects and Contraindication
31.4.5 Drug Interaction
31.4.6 Uses
31.5 Niacin
31.5.1 Mechanism of Action
31.5.2 Effect on Lipoproteins
31.5.3 Pharmacokinetics
31.5.4 Adverse Effect
31.5.5 Use
31.6 Acipimox
31.7 Bile Acid Sequestrants
31.8 Ezetimibe
31.9 Mipomersen
31.10 Lomitapide
31.11 PCSK9 Inhibitors
31.12 Gugulipid
31.13 Other Hypolipidemic Agents Developed but Withdrawn/Failure
31.14 Clinical Pharmacology
Bibliography
Part V: Pulmonary Pharmacology
32: Treatment of Asthma and COPD
32.1 Pathophysiology of Asthma and COPD
32.1.1 Clinical Presentation
32.2 Routes of Drug Administration in Asthma and Pulmonary Diseases
32.3 Drug Classes
32.3.1 Beta-2 Agonists
32.3.2 Corticosteroids
32.3.3 Muscarinic Antagonists
32.3.4 Leukotriene Inhibitors
32.3.5 Methylxanthines and Phosphodiesterase Inhibitors
32.3.6 Mast Cell Stabilizers
32.3.7 Monoclonal Antibody
32.4 Stepwise Management of Bronchial Asthma (Fig. 32.4)
32.5 Management of COPD
Bibliography
33: Drugs Used in Cough and Rhinitis
33.1 Cough
33.1.1 Drugs for Cough Management
33.1.1.1 Antitussives
33.1.1.2 Expectorants (Mucokinetics)
33.1.1.3 Mucolytics
33.1.1.4 Demulcents
33.1.2 Treatment of Specific Types of Cough
33.2 Rhinitis
33.2.1 Drugs for Rhinitis
Bibiliography
Part VI: Gastrointestinal Pharmacology
34: Drugs Used in Acid Peptic Disorders
34.1 Introduction
34.2 Physiology of Acid Secretion and Mucosal Defense Mechanism
34.3 Drugs Used in the Management of Peptic Ulcer
34.3.1 Antacids
34.3.2 Prostaglandin Analogs
34.3.3 Ulcer Protectants
34.3.4 Histamine Receptor (H2) Blockers
34.3.5 Proton Pump Inhibitors (PPIs)
34.3.6 Potassium-Competitive Acid Blockers (P-CAB)
34.3.7 Anti-H. pylori Drugs
34.3.8 Obsolete Anti-Ulcer Drugs
34.3.9 Clinical Pharmacology
Bibliography
35: Drugs Affecting Gastrointestinal Motility
35.1 Introduction
35.2 Regulation of Gastrointestinal Motility by the Enteric Nervous System
Box 35.1: Classification of Drugs Affecting Gastrointestinal Motility
35.3 Prokinetic Agents
35.3.1 Dopamine Receptor Antagonists
35.3.2 Serotonin Receptor Agonists
35.3.3 Motilin and Macrolide Antibiotics
35.3.4 Miscellaneous Agents for Stimulating GI Motility
35.4 Agents Suppressing GI Motility
Bibliography
36: Antiemetics
36.1 Introduction
36.2 Pathophysiology of Emesis
36.3 Pathophysiology of Nausea: An Entity Distinct from Emesis
36.4 Classification of Antiemetics
Box 36.1: Classification of Antiemetics
36.4.1 5HT3 Receptor Antagonists
36.4.2 D2 Dopamine Receptor Blockers
36.4.3 Anticholinergic Agents
36.4.4 Antihistamines
36.4.5 Neurokinin (NK1) Receptor Antagonists
36.4.6 Cannabinoids
36.4.6.1 Dronabinol (Delta-9-Tetrahydrocannabinol, THC)
36.4.6.2 Nabilone
36.4.7 Glucocorticoids
36.4.8 Benzodiazepines
Bibliography
37: Drug Therapy for Constipation
37.1 Introduction
37.2 Mechanism and Etiology of Constipation
37.3 Drugs for Constipation
37.4 Bulk Forming Agents
37.4.1 Bran
37.4.2 Psyllium (Ispaghula)
37.4.3 Methylcellulose
37.5 Stool Softeners (Emollients)
37.5.1 Liquid Paraffin (Mineral Oil)
37.5.2 Dioctyl Sulfosuccinate (DOSS or Docusate)
37.6 Stimulant Purgatives
37.6.1 Bisacodyl
37.6.2 Sodium Picosulfate
37.6.3 Senna and Cascara
37.6.4 Castor Oil
37.7 Osmotic Purgatives (Salts and Lactulose)
37.8 Prokinetics
37.8.1 Prucalopride and Cisapride (5-HT4 Receptors Agonists)
37.8.2 Macrolide Antibiotics (Motilin Agonists)
37.8.3 mu-Opioid Receptor Antagonists
37.9 Active Secretors
37.9.1 Prostaglandin Analogue (Lubiprostone)
37.9.2 Membrane Spanning Guanylate Cyclase-C Receptor Agonists: Linaclotide and Plecanatide
37.10 Clinical Pharmacology
Bibliography
38: Antidiarrheal Agents
38.1 General Definition of Diarrhea
38.2 General Principles in the Treatment of Diarrhea
38.3 Inhibition of Intestinal Motility-Antisecretory Drugs
38.3.1 Opioids
38.3.2 Octreotide and Somatostatin
38.3.3 Enkephalinase Inhibitors
38.3.4 Alpha 2 Agonists
38.3.5 5HT3 Receptor Antagonists
38.3.6 Apical Chloride Channel Inhibitor
38.3.7 Bismuth Subsalicylate
38.3.8 Zinc
38.4 Intraluminal Agents
38.4.1 Clays
38.4.2 Bile Salt Binding Resins
38.4.3 Fiber
38.5 Pro-Absorptive Agents
38.5.1 Teduglutide
38.6 Oral Rehydration Solution
38.7 Treatment of Specific Diarrhea
38.7.1 Secretory Diarrhea in Tumors [Like Carcinoid Syndrome, VIPomas]
38.7.2 Drugs That Are Used in Traveler´s Diarrhea
Bibliography
39: Irritable Bowel Syndrome
39.1 Introduction
39.2 Pathophysiology
39.3 Pharmacotherapy of IBS
39.3.1 Current Pharmacological Treatment for IBS
39.3.1.1 Medications for Abdominal Pain
39.3.1.2 Medications for Diarrhea
39.3.1.3 Medications for Constipation
39.3.1.4 Anti-inflammatory Approaches
39.3.2 Newer Drugs Under Study for IBS
Box 39.1 Medications Used in Management of Irritable Bowel Syndrome
Bibliography
40: Pharmacotherapy of Inflammatory Bowel Disease
40.1 Introduction
40.2 Pharmacological Management of IBD
40.2.1 Aminosalicylates
40.2.2 Corticosteroids
40.2.3 Thiopurines
40.2.4 Methotrexate and Cyclosporine
40.2.5 Novel Therapies for IBD
40.2.5.1 TNF-alpha Inhibitors
40.2.5.2 Anti-IL-12/IL-23 Agents
40.2.5.3 Selective Anti-IL-23 Agents
40.2.5.4 Anti-IL-17 Agents
40.2.5.5 Anti-Adhesion Agents
40.2.5.6 Antibiotics and Probiotics
40.2.5.7 Other Modalities of Pharmacological Management
Bibliography
41: Miscellaneous Drugs Acting on the Gastrointestinal System
41.1 Appetite Stimulants or Orexigenic Drugs
41.1.1 Alcohol as Appetite Stimulant
41.1.2 Drugs as Appetite Stimulants
41.2 Digestants
41.2.1 Pharmacokinetics of Digestants
41.2.2 Scope of Digestants
41.2.3 Adverse Effects of Digestants
41.3 Anti-Flatulence Drugs and Carminatives
Bibliography
Part VII: Endocrine Pharmacology
42: Hypothalamic and Pituitary Hormones
42.1 Introduction
42.2 Anatomy of Hypothalamus-Pituitary
Box 42.1 Classification of Endocrine Hormones Based on the Site of Secretion
Box 42.2 Classification of Hormones Based on Its Site of Binding
42.3 Physiology of Hypothalamus-Pituitary-Organ Axis
42.4 Pathophysiology of Hypothalamus-Pituitary
42.5 Drugs Affecting the Hypothalamus-Pituitary-Organ Axis
42.5.1 Somatostatin Analogues
42.5.2 Pegvisomant
42.5.3 Growth Hormone (Somatropin)
42.5.4 Mecasermin
42.5.5 Drugs for Hyperprolactinemia
42.5.6 GnRH Agonists
Box 42.3 Various Formulations of GnRH Analogues
Box 42.4 Indications for Pulsatile and Non-pulsatile GnRH Therapy
42.5.7 GnRH Antagonists
42.5.8 Recombinant Gonadotropins
42.5.9 Oxytocin
42.5.10 Vasopressin
Box 42.5 Characteristic Features of Vasopressin and Desmopressin
42.5.11 Vasopressin Antagonists
Box 42.6 Characteristic Features of Conivaptan and Tolvaptan
42.5.12 ACTH
42.5.13 TSH
Bibliography
43: Pharmacotherapy of Diabetes Mellitus
43.1 Introduction
43.2 Classification of Diabetes and Diabetes Clusters
43.3 Screening and Diagnosis of DM
43.4 Pathophysiology of Hyperglycemia
43.5 Treatment of DM
43.5.1 Management of Type 1 DM
Box 43.1 Sources of Animal Insulins
Box 43.2 Spectrum of Actions of Insulins
43.5.2 Management of Type 2 DM
43.5.2.1 Guideline Recommendations for T2DM Management
43.5.3 Gestational Diabetes Mellitus (GDM)
Bibliography
44: Thyroid and Antithyroid Drugs
44.1 Introduction
44.2 Thyroid Hormone Chemistry and Biosynthesis
Box 44.1 Major Processes Involved in the Synthesis, Storage, and Secretion of T3 and T4
44.2.1 Iodide Uptake
44.2.2 Oxidation and Iodination
44.2.3 Formation of T4 and T3 from Iodotyrosines (Coupling)
44.2.4 Secretion of Thyroid Hormones
44.2.5 Peripheral Conversion of T4 to T3
44.3 Transport, Metabolism, and Excretion of Thyroid Hormones
44.4 Regulation of Thyroid Hormone Secretion (Fig. 44.2)
44.5 Mechanism of Action of Thyroid Hormone
44.6 Pharmacological Actions of Thyroid Hormone
44.6.1 Growth and Development
44.6.2 Thermogenic Effects
44.6.3 Cardiovascular Effects
44.6.4 Metabolic Effects
44.7 Thyroid Hormone Preparations
44.7.1 Pharmacokinetics of Thyroid Hormone Preparations
44.7.2 Uses of Thyroid Hormone Preparations
44.7.3 Adverse Effects of Thyroid Hormone Preparations
44.8 Antithyroid Drugs and Other Thyroid Inhibitors
44.8.1 Antithyroid Drugs (Thioamides)
Box 44.2 Treatment of Thyroid Storm
44.8.2 Ionic Inhibitors
44.8.3 Iodine and Iodides (Hormone Release Inhibitors)
44.8.4 Radioactive Iodine (Destroyers of Thyroid Tissue)
Bibliography
45: Adrenocorticosteroids and Their Antagonists
45.1 Introduction
45.2 Biosynthesis of Adrenocortical Hormones
45.3 Regulation of Adrenocortical Hormone Secretion
45.4 Pharmacological Actions of Adrenocortical Hormones
45.5 Mechanism of Action at the Cellular Level
45.6 Glucocorticoid and Mineralocorticoid Preparations
45.7 Pharmacokinetics of Steroids
45.8 Uses of Steroids
45.9 Adverse Effects of Steroids
45.10 Contraindications of Steroids
45.11 Inhibitors of ACTH Secretion, Steroidogenesis and Antagonists of Glucocorticoids and Mineralocorticoids
45.11.1 Inhibitors of ACTH Secretion
45.11.2 Inhibitors of Steroidogenesis
45.11.3 Glucocorticoid Antagonist
45.11.4 Mineralocorticoid Antagonists
Bibliography
46: Gonadal Hormones and Their Inhibitors
46.1 Introduction
Box 46.1 Sites of Synthesis of Gonadal Hormones (Estrogens, Progestins, and Androgens)
46.1.1 Estrogens
Box 46.2 Classification of Estrogens
Box 46.3 Preferred Dose of Estrogens (Ethinyl Estradiol) in Different Settings
46.1.2 Actions of Estrogens
46.1.3 Mechanism of Action of Estrogens
46.1.4 Pharmacokinetics of Estrogens
46.1.5 Adverse Drug Reactions Related to Estrogens
46.1.6 Clinical Indications of Estrogens
46.2 Antiestrogens
Box 46.4 Classification of Estrogen Synthesis Inhibitors (Aromatase Inhibitors)
Box 46.5 Classification of Antioestrogens
46.2.1 Clomiphene Citrate
46.2.2 Fulvestrant
46.2.3 Letrozole
46.3 Selective Estrogen Receptor Modulators (SERMs)
Box 46.6 Classification of Selective Estrogen Receptor Modulators (SERMs)
46.3.1 Tamoxifen Citrate
46.3.2 Raloxifene
46.4 Progestins
Box 46.7 Classification of Progestins/Progestational Agents/Progestagens/Progestogens/Gestagens/Gestogens
46.4.1 Actions of Progestins
Box 46.8 Progestins with Androgenic Actions
46.4.2 Mechanism of Action of Progestins
46.4.3 Pharmacokinetics of Progestins
46.4.4 Adverse Drug Reactions Related to Progestins
46.4.5 Clinical Indications of Progestins
46.5 Antiprogestins
Box 46.9 Classification of Antiprogestins
46.5.1 Mifepristone
46.5.2 Ulipristal
46.6 Birth Controlling Measures in Females
46.6.1 Oral Contraceptive Pills (OCPs)
Box 46.10 Overview of Preparations of Oral Contraceptive Pills (OCPs)
Box 46.11 Mechanism of Action of Oral Contraceptive Pills (OCPs)
Box 46.12 ADRs Associated with Estrogen and Progestin Components in OCPs
Box 46.13 Incidence of Thromboembolic Events
Box 46.14 Major Risks and Benefits of Oral Contraceptive Pills (OCPs) [Containing Both The Components (Estrogens and Progestin...
Box 46.15 Mechanism of Common ADRs Associated with Both Components (Estrogen and Progestin) in OCPs
Box 46.16 Contraindications of Oral Contraceptive Pills (OCPs)
Box 46.17 Salient Updates on Hormone Replacement Therapy (HRT)
46.7 Androgens
Box 46.18 Classification of Androgens
46.7.1 Androgen Actions
46.7.2 Mechanism of Action
46.7.3 Pharmacokinetics of Androgens
46.7.4 Adverse Drug Reactions Related to Androgens
46.7.5 Clinical Indications of Androgens
46.8 Antiandrogens
Box 46.19 Classification of Antiandrogens
46.9 Conclusion
Bibliography
47: Pharmacotherapy of Obesity
47.1 Introduction
47.2 Physiology of Appetite and Satiety
47.3 Drugs Used to Treat Obesity
47.3.1 Lorcaserin
47.3.2 Phentermine and Phentermine-Topiramate Fixed Drug Combination (FDC)
47.3.3 Liraglutide
47.3.4 Naltrexone-Bupropion FDC
47.3.5 Orlistat
47.3.6 Obsolete Drugs Used for Obesity
47.4 Clinical Pharmacology
Bibliography
48: Drugs Affecting Bone Mineral Homeostasis
48.1 Introduction
48.2 Hormonal Regulation of Bone Mineral Homeostasis
48.2.1 Vitamin D
Box 48.1 Management of Vitamin D Deficiency and Insufficiency
48.2.2 Parathormone (PTH)
48.2.3 Calcitonin
48.2.4 Glucocorticoids
48.2.5 Estrogens
48.3 Non-Hormonal Agents Regulating Bone Mineral Homeostasis
48.3.1 Bisphosphonates
48.3.2 Denosumab
Bibliography
Part VIII: Hematopoietic System
49: Pharmacotherapy of Iron Deficiency and Other Related Anaemia
49.1 Brief Pathogenesis
49.2 Therapeutic Objectives
49.3 Oral Iron Therapy
Box 49.1 Oral Iron Preparations
49.3.1 Pharmacokinetics
49.3.2 Dosage Calculation
49.3.3 Adverse Effects of Oral Iron Therapy
49.4 Parenteral Iron Therapy
49.4.1 Indications of Parenteral Iron Therapy
49.4.2 Preparations for Parenteral Use
Box 49.2 Parenteral Iron Preparations
49.4.3 Calculating the Dose Required
49.4.4 Adverse Drug Reactions
49.5 Long-Term Considerations of Iron Therapy
49.6 Key Principles in Pharmacotherapy of Iron Deficiency of Anaemia
49.7 Treatment of Hypoproliferative Anaemia
49.7.1 Erythropoietin (Erythropoiesis Stimulating Agents)
Bibliography
50: Pharmacotherapy of Vitamin B12 and Folic Acid Deficiency
50.1 Introduction
50.2 Vitamin B12 (Cobalamin)
50.2.1 Chemistry
50.2.2 Source and Requirements
50.2.3 Absorption, Transport, and Storage
50.2.4 Biochemical Role
50.2.5 Drugs Causing Cobalamin Deficiency
50.2.6 Preparations of Cobalamin
50.2.7 Uses of Cobalamin
50.3 Folic Acid
50.3.1 Chemistry
50.3.2 Absorption and Excretion
50.3.3 Biochemical Role of THFA
50.3.4 Source and Daily Requirements
50.3.5 Drugs Interfering with Folate Metabolism
50.3.6 Uses
50.4 Clinical Pharmacology
Bibliography
51: Drug-Induced Blood Dyscrasias
51.1 Hemolytic Anemia (Borham 2018)
51.1.1 Immune-Mediated Haemolytic Anemia (IHA)
51.1.2 Non-Immune-Mediated Hemolytic Anemia (Borham 2018)
51.2 Aplastic Anemia (Qahtani 2018)
Box 51.1 Drugs Causing Aplastic Anemia
51.3 Megaloblastic Anemia (Qahtani 2018; Borham 2018)
51.4 Sideroblastic Anemia (Mintzer et al. 2009)
Box 51.2 Drugs Causing Sideroblastic Anemia
51.5 Methemoglobinemia (Mintzer et al. 2009)
Box 51.3 Drugs Causing Methemoglobinemia
51.6 Pure Red Cell Aplasia (Mintzer et al. 2009)
Box 51.4 Drugs Causing Pure Red Cell Aplasia
51.7 Immune Thrombocytopenia (Mintzer et al. 2009)
Box 51.5 Drugs Associated with Immune Thrombocytopenia
51.8 Thrombotic Microangiopathies (Mintzer et al. 2009)
Box 51.6 Drugs Associated with Thrombotic Microangiopathies
51.9 Hypercoagulability (Mintzer et al. 2009)
Box 51.7 Drugs Causing Hypercoagulability
51.10 Hypoprothrombinemia (Mintzer et al. 2009)
Box 51.8 Drugs Causing Hypoprothombinemia
51.11 Agranulocytosis/Neutropenia (Mintzer et al. 2009)
51.12 Neutrophilia (Mintzer et al. 2009)
Box 51.9 Drugs Causing Neutrophilia
51.13 Eosinophilia (Mintzer et al. 2009)
Box 51.10 Drugs Causing Eosinophilia
51.14 Polycythemia (Mintzer et al. 2009)
51.15 Myelodysplasia and Acute Leukemia (Mintzer et al. 2009)
Box 51.11 Drugs Causing Myelodysplastic Syndrome
Bibliography
Part IX: Chemotherapy of Microbial Diseases
52: General Principles of Antimicrobial Therapy
52.1 Introduction
52.2 Classification of Antimicrobial Agents
52.3 Antibacterial Agents
52.3.1 Pharmacodynamic Parameters
52.3.2 Pharmacokinetic Parameters of Antimicrobial Therapy
52.3.3 Barriers to Drug Penetration
52.3.4 Concentration vs Time Dependent Killing
52.4 Antiviral Agents
52.5 Antifungal and Antiprotozoal Agents
52.6 Selection of Appropriate Antimicrobial Agents
52.7 Types of Antimicrobial Therapy (Fig. 52.3)
52.7.1 Chemoprophylaxis
52.7.1.1 Immunocompromised Patients
52.7.1.2 Surgical Prophylaxis
52.7.1.3 Prophylaxis for Infective Endocarditis
52.7.1.4 Pre- and Post-Exposure Prophylaxis
52.7.1.5 Suppressive Prophylaxis
52.7.2 Empirical Treatment
52.7.3 Definitive Therapy
52.8 Combination Therapy
52.9 Problems Encountered in Antimicrobial Therapy
52.9.1 Resistance to Therapy
52.9.1.1 Mechanism of Drug Resistance
52.9.1.2 Types of Drug Resistance
52.9.2 Adverse Drug Reactions
52.9.3 Super Infection and Masking of Infection
Bibilography
53: Sulfonamides, Quinolones, and Agents for Urinary Tract Infections
53.1 Sulphonamides
53.1.1 Classification of Sulphonamides
Box 53.1 Classification of Sulphonamides (Values in Parentheses Indicate the Half-Lives)
53.1.2 Chemical Nature of Sulphonamides
53.1.3 Mechanism of Action of Sulphonamides
53.1.4 Antibacterial Spectrum of Sulphonamides
53.1.5 Pharmacokinetics of Sulphonamides
53.1.6 Clinical Uses of Sulphonamides
53.1.7 Adverse Effects of Sulphonamides
53.1.8 Drugs Interactions of Sulphonamides
53.1.9 Sulphonamide Resistance
53.1.10 Key Points on Individual Sulphonamides
Box 53.2 Characteristics of Individual Sulphonamide Agents
53.2 Cotrimoxazole/Trimethoprim-Sulphamethoxazole
53.2.1 Mechanism of Action of Cotrimoxazole
53.2.2 Antibacterial Spectrum of Cotrimoxazole
53.2.3 Clinical Uses of Cotrimoxazole
53.2.4 Adverse Effects of Cotrimoxazole
53.2.5 Cotrimoxazole Resistance
53.3 Quinolones
53.3.1 Mechanism of Action of Quinolones
53.3.2 Antibacterial Spectrum of Quinolones
53.3.3 Classification of Quinolones
Box 53.3 Modern Classification of Quinolones
53.3.4 Pharmacokinetics of Quinolones
53.3.5 Clinical Uses of Quinolones
53.3.6 Adverse Effects of Quinolones
53.3.7 Quinolone Resistance
53.3.8 Key Points on Individual Quinolones
Box 53.4 Characteristics of Individual Quinolone Agents
53.4 Other Agents for Urinary Tract Infections
53.4.1 Urinary Antiseptics
53.4.2 Urinary Analgesics
Bibliography
54: Penicillins, Cephalosporins, and Other beta-Lactam Antibiotics
54.1 Penicillins
54.2 Cephalosporins and Cephamycins
54.2.1 First-Generation Cephalosporins
54.2.2 Second-Generation Cephalosporins
54.2.3 Third-Generation Cephalosporins
54.2.4 Fourth-Generation Cephalosporins
54.3 Carbapenams
54.4 Monobactams
54.5 Carbacepham
54.6 beta-Lactamase Inhibitors
Bibliography
55: Protein Synthesis Inhibitors
55.1 Introduction
55.2 Aminoglycosides
55.2.1 Sources of Aminoglycosides
Box 55.1 Sources of Aminoglycoside Antibiotics and their Nomemclature
55.2.2 Chemistry and Nomenclature
55.2.3 Mechanism of Action
55.2.4 Spectrum of Anti-Microbial Activity
55.2.5 Mechanism of Resistance
55.2.6 Salient Pharmacokinetic Features
55.2.7 Dosing and Monitoring
55.2.8 Therapeutic Uses
55.2.9 Adverse Effects
55.2.10 Salient Pharmacological Properties of Individual Aminoglycosides
55.3 Tetracyclines and Glycylcyclines
55.3.1 Sources of Tetracyclines and Glycylcyclines
55.3.2 Mechanism of Action
55.3.3 Spectrum of Anti-Microbial Activity
55.3.4 Mechanism of Resistance
55.3.5 Salient Pharmacokinetic Features
55.3.6 Dosing and Monitoring
55.3.7 Therapeutic Uses
55.3.8 Adverse Effects
55.4 Chloramphenicol
55.4.1 Mechanism of Action (Fig. 55.5)
55.4.2 Spectrum of Anti-Microbial Activity
55.4.3 Mechanism of Resistance
55.4.4 Salient Pharmacokinetic Features
55.4.5 Therapeutic Uses and Dosage
55.4.6 Adverse Effects
55.5 Macrolides and Ketolides
55.5.1 Mechanism of Action
55.5.2 Spectrum of Anti-Microbial Activity
55.5.3 Mechanism of Resistance
55.5.4 Salient Pharmacokinetic Features
Box 55.2 Salient Pharmacokinetic Features of Various Macrolide and Ketolide Antibiotics
55.5.5 Therapeutic Uses and Dosage
Box 55.3 Drug Dosages of Various Macrolide and Ketolide Antibiotics
55.5.6 Adverse Effects
55.5.7 Drug Interactions
55.6 Lincosamides
55.6.1 Mechanism of Action
55.6.2 Spectrum of Anti-Microbial Activity
55.6.3 Mechanism of Resistance
55.6.4 Salient Pharmacokinetic Features
55.6.5 Dosing
55.6.6 Therapeutic Uses
55.6.7 Adverse Effects
55.7 Streptogramins
55.7.1 Mechanism of Action
55.7.2 Spectrum of Anti-Microbial Activity
55.7.3 Mechanism of Resistance
55.7.4 Salient Pharmacokinetic Features
55.7.5 Therapeutic Uses and Dosage
55.7.6 Adverse Effects
55.7.7 Drug Interactions
55.8 Oxazolidinones
55.8.1 Mechanism of Action
55.8.2 Spectrum of Anti-Microbial Activity
55.8.3 Mechanism of Resistance
55.8.4 Salient Pharmacokinetic Features
55.8.5 Dosing
55.8.6 Therapeutic Uses
55.8.7 Adverse Effects
55.8.8 Drug Interactions
55.9 MiscellaneousDrugs
55.9.1 Spectinomycin
55.9.2 Mupirocin
55.9.3 Fusidic Acid
55.9.4 Pleuromutilins
Bibliography
56: Antimycobacterial Drugs
56.1 Introduction
56.1.1 Epidemiology
56.1.2 Etiopathogenesis
56.1.3 Clinical Presentation
56.1.4 Diagnosis
56.1.4.1 Microscopy
56.1.4.2 Culture
56.1.4.3 Molecular Methods
56.1.4.4 Serology
56.1.4.5 Tuberculin Skin Test
56.1.4.6 Chest Radiography
56.1.5 Drugs for Tuberculosis
56.1.5.1 First-Line Antituberculosis Drugs
56.1.5.2 Second-Line Antituberculosis Drugs
56.1.5.3 Drug Susceptibility Testing (DST)
56.1.6 Treatment of Tuberculosis
56.1.6.1 Treatment of Drug-Resistant TB
56.1.6.2 Treatment of Extrapulmonary Tuberculosis
56.1.6.3 Treatment of Tuberculosis in HIV-Positive Persons
56.1.6.4 Treatment of TB in Pregnant or Lactating Women
56.1.6.5 Treatment of TB in Children
56.1.6.6 Treatment of Latent TB
56.1.7 Tuberculosis Infection Prevention and Control
56.2 Drugs for Leprosy
56.2.1 Epidemiology
56.2.2 Etiopathogenesis
56.2.3 Clinical Presentation
56.2.4 Diagnosis
56.2.5 Drugs for Leprosy
56.2.5.1 Multidrug Therapy (MDT)
56.2.5.2 Treatment of Leprosy Reactions
56.2.5.3 Chemoprophylaxis for Leprosy
56.3 Drugs for Nontuberculous Mycobacteria
56.4 Conclusion
Bibliography
57: Antifungal Drugs
57.1 Introduction
57.2 Amphotericin B
57.2.1 Mechanism of Action
57.2.2 Pharmacokinetics
57.2.3 Spectrum of Activity
57.2.4 Therapeutic Uses
57.2.5 Adverse Effects
57.3 Imidazoles and Triazoles
57.3.1 Mechanism of Action
57.3.2 Pharmacokinetics
57.3.3 Spectrum of Activity
57.3.4 Therapeutic Uses
57.3.4.1 Fluconazole (Most Commonly Used Azole)
57.3.4.2 Itraconazole
57.3.4.3 Voriconazole
57.3.4.4 Posaconazole
57.3.4.5 Isavuconazole
57.3.5 Adverse Effects
57.3.5.1 Fluconazole
57.3.5.2 Itraconazole
57.3.5.3 Voriconazole
57.3.5.4 Posaconazole
57.3.5.5 Isavuconazole
57.4 Flucytosine
57.4.1 Mechanism of Action
57.4.2 Pharmacokinetics
57.4.3 Spectrum of Activity
57.4.4 Therapeutic Uses
57.4.5 Adverse Effects
57.5 Echinocandins
57.5.1 Mechanism of Action
57.5.2 Pharmacokinetics
57.5.3 Spectrum of Activity
57.5.4 Therapeutic Uses
57.5.4.1 Caspofungin
57.5.4.2 Micafungin
57.5.4.3 Anidulafungin
57.5.5 Adverse Effects
57.6 Griseofulvin
57.6.1 Mechanism of Action
57.6.2 Pharmacokinetics
57.6.3 Spectrum of Activity
57.6.4 Therapeutic Uses
57.6.5 Adverse Effects
57.7 Terbinafine
57.7.1 Mechanism of Action
57.7.2 Pharmacokinetics
57.7.3 Spectrum of Activity
57.7.4 Therapeutic Uses
57.7.5 Adverse Effects
57.8 Topical Antifungals
57.8.1 Topical Azoles
57.8.1.1 Ketoconazole
57.8.1.2 Clotrimazole
57.8.1.3 Miconazole
57.8.2 Topical Allylamines
57.8.3 Miscellaneous
57.8.3.1 Nystatin
57.8.3.2 Haloprogin
57.8.3.3 Tolnaftate
57.8.3.4 Undecylenic Acid
57.8.3.5 Ciclopirox Olamine
57.8.3.6 Tavaborole
57.8.3.7 Benzoic and Salicylic Acids
57.9 Conclusion
Bibliography
58: Antiviral Drugs
58.1 Anti-Influenza Drugs
58.1.1 Introduction
58.1.2 Structure of Influenza Virus (Fig. 58.1)
58.1.3 Anti-Influenza Drug Classification
58.1.4 Viral RNA Replication and its Inhibitors (Fig. 58.2)
58.1.5 Prophylaxis for INFLUENZA INFECTION
58.1.6 M2 Protein Inhibitors (Adamantanes)
58.1.7 Neuraminidase Inhibitors
58.1.7.1 Oseltamivir
58.1.7.2 Zanamivir
58.1.7.3 Peramivir
58.1.7.4 Laninamivir Octanoate
58.1.8 Newer Drugs
58.2 Anti-Herpetic Drugs
58.2.1 Introduction
58.2.2 Steps of Viral DNA Replication and its Inhibitors (Fig. 58.3)
58.2.3 Classification of Anti-Herpetic Drugs
58.2.4 Attachment Inhibitor
58.2.5 Entry Inhibitor
58.2.6 DNAP α and Thymidine Kinase Inhibitors
58.2.7 DNAP delta, epsi Inhibitor
58.2.8 Newer Drugs
58.2.9 Therapeutics
58.3 Anti-Retroviral Drugs
58.3.1 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Box 58.1 Nucleic Acid Analogues
58.3.1.1 Salient Features
58.3.2 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
58.3.3 HIV Protease Inhibitors
58.3.4 Fusion/Entry Inhibitors
58.3.5 Integrase Inhibitors (IIs) or Integrase Strand Transfer Inhibitors (INSTIs)
58.3.6 Therapeutic Guidelines (Based on NACO Guidelines, October 2018)
58.3.6.1 HIV and TB
58.3.6.2 HIV in Pregnancy
58.3.6.3 Post-Exposure Prophylaxis
58.3.7 HIV Vaccines
58.4 Anti-Hepatitis Drugs
58.4.1 Introduction
58.4.2 Currently Available Therapies
58.4.3 Genotypes in Viral Hepatitis
58.4.4 Structure and Pathogenesis
58.4.5 Initiation of Therapy in HBV (Table 58.4)
58.4.6 Classification of Drugs Used in Hepatitis
58.4.7 Anti-Hepatitis-B Drugs
58.4.7.1 Interferonα
58.4.7.2 Lamivudine
58.4.7.3 Adefovir Dipivoxil
58.4.7.4 Entecavir
58.4.7.5 Telbivudine
58.4.7.6 Tenofovir
58.4.8 Stoppage of Therapy
58.4.9 Clinical Implication
58.4.10 Anti-Hepatitis C Drugs
58.4.10.1 Ribavirin
58.4.10.2 Directly Acting Antiviral Agents (DAAs) for Hepatitis C
NS3/4A Protease Inhibitors
NS5B Nucleoside and Non-Nucleoside Polymerase Inhibitors
NS5A Inhibitors
58.4.10.3 Therapeutic Aspects
Bibliography
59: Miscellaneous Antimicrobial Agents
59.1 Introduction
59.2 Glycopeptide Antibiotics
59.2.1 Vancomycin
59.2.2 Teicoplanin
59.2.3 Other Glycopeptide Drugs
59.3 Polypeptide Antibiotics
59.3.1 Polymyxin B and Colistin (Polymyxin E)
59.3.2 Bacitracin
59.4 Urinary Antiseptics
59.4.1 Nitrofurantoin
59.4.2 Methenamine
59.5 Antiseptics, Disinfectants, and Sterilants
59.5.1 Alcohols
59.5.2 Aldehydes
59.5.3 Halogens
59.5.4 Phenolics
59.5.5 Oxidizing Agents
59.6 Management of Sexually Transmitted Diseases (STDs)
59.6.1 Principles of Management of STD
59.6.2 Common Presentations of STD
59.6.2.1 Anogenital Ulcer
59.6.2.2 Urethritis
59.6.2.3 Vaginitis
Box 59.1 Treatment for Vaginosis During Pregnancy
59.6.2.4 Pelvic Inflammatory Disease (PID)
59.6.2.5 Genital Warts
Bibliography
60: Chemotherapy of Malaria and Other Protozoal Diseases
60.1 Introduction
60.1.1 Historical Perspectives of Malaria
60.1.2 Antimalarials Therapeutic Agents
Box 60.1: Antimalarial Drugs Grouped Based on Elimination Half-Life (t1/2)
60.1.2.1 Quinine
60.1.2.2 Chloroquine
60.1.2.3 Sulfadoxine-Pyrimethamine
60.1.2.4 Mefloquine
60.1.2.5 Amodiaquine
60.1.2.6 Piperaquine
60.1.2.7 Primaquine
60.1.2.8 Mepacrine
60.1.2.9 Pyronaridine
60.1.2.10 Atovaquone-Proguanil
60.1.2.11 Halofantrine
60.1.2.12 Lumefantrine
60.1.2.13 Tetracycline and Doxycycline
60.1.2.14 Clindamycin
60.1.2.15 Artemisinin
60.1.2.16 Artemisinin Derivatives
60.1.2.17 Artemisinin Combination Therapy (ACTs)
60.1.2.18 Tafenoquine
60.1.3 Chemotherapeutic Regimens of Uncomplicated P. falciparum Malaria
Box 60.2: Therapeutic Regimens for Uncomplicated P. falciparum Malaria in Nonpregnant Adults and Children
60.1.4 Antimalarial Regimen for Severe Malaria
Box 60.3: Therapeutic Regimens for Severe Malaria
60.1.5 Other Therapeutic Regimens for Uncomplicated Malaria
60.1.6 Chemoprevention of Malaria Among High-Risk Group in Endemic Areas and Seasonal Prevention of Malaria
60.1.6.1 Chemoprophylaxis Among Travelers
60.1.6.2 Chemoprophylaxis in Pregnant and Children Travelers
60.1.6.3 Standby Emergency Treatment (SBET)
60.1.7 Antimalarial Therapeutics: Future Perspectives
60.1.7.1 Artemisinin and Partner Drug Resistance
60.1.7.2 Mass Drug Administration to Control Vector Transmission of Malaria
60.1.7.3 Malaria Vaccine
60.1.7.4 Investigational Drugs in Clinical Development
60.2 Babesiosis
60.3 Trypanosomiasis
60.3.1 Human African Trypanosomiasis (HAT) (Sleeping Sickness)
60.3.1.1 Pentamidine
60.3.1.2 Eflornithine
60.3.1.3 Nifurtimox-eflornithine combination therapy (NECT)
60.3.1.4 Suramin
60.3.1.5 Melarsoprol
60.3.2 American Trypanosomiasis (Chagas Disease)
60.4 Leishmaniasis
60.4.1 Amphotericin B
60.4.2 Pentavalent Antimonials
60.4.3 Miltefosine
60.4.4 Paromomycin
60.4.5 Combination of Drugs for Visceral Leishmaniasis
60.4.6 Topical Therapy for Cutaneous Leishmaniasis
60.5 Coccidiosis
60.6 Blastocystis
60.7 Amebiasis
60.7.1 Nitroimidazoles: Metronidazole
60.7.2 Thiazolides
60.7.3 Emetine and Its Derivatives
60.7.4 Chloroquine
60.7.5 Diloxanide Furoate
60.7.6 Paromomycin
60.7.7 Iodoquinol and Quiniodochlor
60.8 Giardiasis
60.8.1 Nitazoxanide
60.9 Trichomoniasis
60.10 Toxoplasmosis
60.11 Naegleria
60.12 Acanthamoeba
60.13 Dientamoeba
60.14 Balantidium
References
61: Chemotherapy of Helminthiasis
61.1 Anthelminthic Drugs
61.1.1 Praziquantel
61.1.2 Triclabendazole
61.1.3 Thiabendazole
61.1.4 Mebendazole
61.1.5 Albendazole
61.1.6 Diethylcarbamazine Citrate (DEC)
61.1.7 Tribendimidine
61.1.8 Ivermectin
61.2 Helminthiasis: Presentation and Therapeutic Regimens
61.2.1 Trematodes
61.2.1.1 Schistosomiasis (Bilharsiasis)
61.2.1.2 Opisthorchiasis
61.2.1.3 Fascioliasis
61.2.1.4 Paragonimiasis
61.2.2 Cestodes
61.2.2.1 Noninvasive Infections
61.2.2.2 Tissue Infections
Cysticercosis
Echinococcosis
61.2.3 Nematodes
61.2.3.1 Ascariasis
61.2.3.2 Trichuriasis
61.2.3.3 Hookworm Infections
61.2.3.4 Strongyloidiasis
61.2.3.5 Enterobiasis
61.2.3.6 Soil-Transmitted Helminths (STH)
61.2.3.7 Invasive Nematode Infections
Trichinosis, Toxocariasis, and Cutaneous Larva Migrans
61.2.3.8 Filariasis
61.2.3.9 Onchocerciasis
61.2.3.10 Loiasis
61.2.3.11 Dracunculiasis (Guinea-Worm Disease)
Bibliography
Part X: Pharmacotherapy of Neoplastic Diseases
62: General Principles of Cancer Chemotherapy
62.1 Terminologies
62.2 Cell Cycle
62.2.1 Phases of Cell Cycle
62.2.2 Clinical Importance of Phases
62.2.3 Classification of Cancer Chemotherapy Agents
62.2.4 Effect of Anticancer Agents on Cell Cycle Kinetics
62.2.4.1 Murine L1210 Leukaemia Model
62.2.4.2 Gompertzian Model
62.3 Combination Chemotherapy
62.3.1 Principles of Combining Anticancer Drugs for Combination Chemotherapy
62.4 Drug Resistance
62.4.1 Primary Resistance (Develops before Exposure to the Anticancer Agents)
62.4.2 Acquired Resistance (Develops with Exposure to Anticancer Agents)
62.4.3 Molecular Mechanisms Involved in the Development of Acquired Resistance
62.5 Toxicity
62.6 General Toxicity
62.6.1 Haematopoietic System
62.6.2 Gastrointestinal System
62.6.2.1 Nausea and Vomiting
Phases of Vomiting
Management of Breakthrough or Refractory Nausea and Vomiting
Management of Anticipatory Nausea and Vomiting
Antiemetic Agents
62.6.2.2 Mucositis
Oral Mucositis
Gastrointestinal Mucositis
Drugs Causing Mucositis
Management
62.6.2.3 Constipation
Management
62.6.2.4 Diarrhoea
Management
62.6.3 Nervous System Toxicity
Box 62.1 Anticancer Drugs Causing Neurotoxicity
62.6.3.1 Prevention and Management
62.6.4 Metabolic Abnormalities
62.6.4.1 Drugs Causing Metabolic Abnormalities
62.6.4.2 Management
62.6.5 Hepatic Toxicity
62.6.5.1 Drugs Causing Hepatotoxicity
62.6.5.2 Management
62.6.6 Cardiac Toxicity
62.6.6.1 Prevention and Management
62.6.7 Renal Toxicity
62.6.7.1 Drugs Causing Renal Toxicity
62.6.7.2 Prevention and Management
62.6.8 Bladder and Urinary Toxicity
62.6.8.1 Drugs Causing Bladder and Urinary Tract Toxicity
62.6.8.2 Prevention and Management
62.6.9 Pulmonary Toxicity
Box 62.2 Drugs Causing Pulmonary Toxicity
62.6.9.1 Management
62.6.10 Reproductive System
62.6.10.1 Drugs Causing Infertility
62.6.10.2 Prevention and Management
62.6.11 Carcinogenicity
62.6.11.1 Drugs Causing Secondary Cancers
62.6.12 Dermatological Toxicity
62.6.12.1 Chemotherapy-Induced Alopecia
Box 62.3 Anticancer Drugs Causing Alopecia
Prevention and Management
62.6.12.2 Hyperpigmentation and Nail Changes
Drugs Causing Hyperpigmentation and Nail Changes
62.6.12.3 Hand-Foot Syndrome [Palmar-Plantar Erythrodysaesthesia (PPE)]
Drugs Causing Hand-Foot Syndrome
Prevention and Management
62.6.13 Ocular Toxicity
62.6.13.1 Drugs Causing Ocular Toxicity
62.6.13.2 Prevention and Management
62.6.14 Ototoxicity
62.6.14.1 Drugs Causing Hearing Loss
62.6.14.2 Prevention and Management
62.7 Toxicity Amelioration (Table 62.11)
Bibliography
63: Cytotoxic Drugs
63.1 Introduction
63.2 Classification and Mechanism of Action
63.2.1 Alkylating Agents
Box 63.1 Classification of Alkylating Agents
63.2.2 Antimetabolites
Box 63.2 Classification of Antimetabolites
63.2.2.1 Mechanism of Action
Folate Analogues/Antagonists
Pyrimidine Analogues
Cytidine Analogues
Purine Analogues
63.2.3 Natural Products and Miscellaneous Drugs
Box 63.3 Classification of Natural Products and Miscellaneous Drugs
63.2.3.1 Mechanism of Action
Microtubule-Damaging Agents
Camptothecin Analogues
Epipodophyllotoxins
Anticancer Antibiotics
Miscellaneous
63.3 Indications and Pharmacokinetics
63.4 Adverse Drug Reactions (ADRs)
Bibliography
64: Targeted Chemotherapy
64.1 Drugs Targeting the Growth Receptors and Downstream Signalling
64.1.1 EGFR Inhibitors
64.1.1.1 Drugs that Block the Receptor (Box 64.1)
Box 64.1 Monoclonal Antibodies that Block the EGFR Receptor
64.1.1.2 Protein Tyrosine Kinase Inhibitors of EGFR
Box 64.2 Tyrosine Kinase Inhibitors of EGFR
64.1.1.3 Osimertinib
64.1.2 HER2/Neu Inhibitors
Box 64.3 Drugs that Block the Activation of Her2/Neu or Tyrosine Kinase Activation
64.1.2.1 Important Note of Adverse Drug Reactions
64.1.3 Monoclonal Antibody to the PDGFR (Platelet-Derived Growth Factor Receptor)
64.1.3.1 Olaratumab
64.1.4 Hedgehog Pathway Inhibitors
64.2 Drugs that Inhibit Intracellular Kinases
64.2.1 Inhibitors of RAF Kinase
Box 64.4 RAF Kinase Inhibitors
64.2.2 Inhibitors of MEK
Box 64.5 MEK Inhibitors
64.2.2.1 Other MEK Inhibitors in Development
64.2.3 Jak-Stat Inhibitors
64.2.4 BCR-ABL Inhibitors
Box 64.6 BCR-ABL Inhibitors
64.3 Drugs that Inhibit Tumor Angiogenesis
64.3.1 Inhibitors of the VEGF and VEGF Pathway
Box 64.7 VEGF and VEGF Pathway Inhibitors
64.3.2 VEGFR Kinase Inhibitors
64.4 Drugs that Alter the Immune Function (Box 64.8)
Box 64.8 Drugs Modulating the Immune Function
64.5 Drugs Acting on Miscellaneous Targets (Box 64.9)
Box 64.9 Drugs with Other Targets
Bibliography
65: Hormonal Agents in the Pharmacotherapy of Cancer
65.1 Historical Timeline
65.2 Hormonal Management of Breast Cancer
65.2.1 Selective Estrogen Receptor Modulators (SERMs)
65.2.2 Aromatase Inhibitors
65.2.3 Indications for Hormone Therapy in Breast Cancer
65.3 Hormonal Management of Prostate Cancer
65.3.1 Androgen Deprivation Therapy
65.3.2 Gonadotropin-Releasing Hormone (GnRH) Agonists
65.3.3 GnRH Antagonists
65.3.4 Combined Androgen Blockade
65.3.5 Intermittent Androgen Deprivation Therapy
65.4 Resistance to Hormonal Therapy
Bibliography
Part XI: Miscellaneous Topics
66: Immunopharmacology
66.1 Immunosuppressants
66.1.1 Adrenocortical Steroids: Glucocorticoids
66.1.2 Calcineurin Inhibitors: Cyclosporine and Tacrolimus (FK506)
66.1.3 Cytotoxic Agents: Azathioprine, Mycophenolate Mofetil, Cyclophosphamide, and Methotrexate
66.1.3.1 Azathioprine
66.1.3.2 Mycophenolate Mofetil (MMF)
66.1.3.3 Fingolimod (FTY720)
66.1.4 Antibodies
66.1.4.1 Polyclonal Antibodies
66.1.4.2 Monoclonal Antibodies
Anti-CD3 Monoclonal Antibodies
Anti-IL-2 Receptor (Anti-CD 25) Antibodies: Daclizumab and Basiliximab
Anti-CD 52 Monoclonal Antibody: Alemtuzumab
Anti-TNF Agents: Infliximab, Adalimumab, and Etanercept
Interleukin 1 Receptor Antagonist: Anakinra, Canakinumab, and Rilonacept
Lymphocyte Function Associated Antigen-1 [LFA-1] Inhibition: Efalizumab and Alefacept
66.1.5 mTOR Inhibitors: Sirolimus and Everolimus
66.1.5.1 Sirolimus (Rapamycin)
66.1.5.2 Everolimus
66.2 Tolerogens
66.2.1 Co-Stimulation Blockade
66.2.2 Donor Cell Chimerism
66.2.3 Soluble HLA
66.2.4 Antigens
66.3 Immunostimulants
66.3.1 Levamisole
66.3.2 Thalidomide
66.3.3 Lenalidomide
66.3.4 Bacillus Calmette Guerin (BCG)
66.3.5 Recombinant Cytokines: Interferons and Interleukins
66.3.5.1 Interferons
66.3.5.2 Aldesleukin
Bibliography
67: Dermatological Pharmacology
67.1 Introduction
67.1.1 Dermal Pharmacokinetics
67.1.2 Vehicles and Dermatological Formulations
67.2 Selective Topical Preparations
67.2.1 Melanizing and Demelanizing Agents
67.2.2 Sunscreens
67.2.3 Antihistamines or Antipruritic Agents
67.2.4 Photochemotherapy
67.2.5 Topical Steroids
Box 67.1 Topical Corticosteroid Formulations Available and Classified Based on Potency
Box 67.2 Skin Disorders Ranked in Order of Sensitivity and Responsiveness to Steroids
67.2.6 Keratolytics
67.2.7 Retinoids
Box 67.3 Topical and Systemic Retinoids and their Clinical Uses
67.3 Drugs for Psoriasis
Box 67.4 Biological Agents for Psoriasis
67.4 Topical Anti-Infective Agents
67.4.1 Topical Antibacterial Agents
67.4.1.1 Mupirocin
67.4.1.2 Retapamulin
67.4.1.3 Bacitracin, Neomycin, and Polymyxin B
67.4.1.4 Gentamicin
67.4.1.5 Silver Sulfadiazine
67.4.1.6 Mafenide
67.4.2 Management of Common Bacterial Skin Infections
67.4.2.1 Drugs for Acne Vulgaris
67.4.2.2 Impetigo
67.4.2.3 Furuncle or Boil
67.4.3 Topical Antiviral Agents
67.4.3.1 Acyclovir
67.4.4 Management of Common Viral Skin Infections
67.4.5 Topical Antifungal Agents
Box 67.5 Topical Antifungals and FDA Approved Indications
67.4.6 Topical Agents for Infestations
Box 67.6 Topical Agents for Parasitic Infestations, their Target Parasites, and the Mechanism of Action
67.4.7 Drugs Affecting Hair Growth (Treatment of Androgenic Alopecia)
67.4.7.1 Minoxidil
67.4.7.2 Finasteride
67.4.7.3 Spironolactone
67.4.8 Miscellaneous Cytotoxic, Immunosuppressant, and Immunomodulatory Agents in Skin Disorders
Bibliography
68: Ocular Pharmacology
68.1 Pharmacokinetic Considerations
68.1.1 Drug Formulation
68.1.2 Absorption into the Eye
68.1.3 Distribution
68.1.4 Metabolism
68.2 Chemotherapeutic Drugs in the Eye
68.2.1 Bacterial Infections (Box 68.1)
Box 68.1 Antibiotics Used in Bacterial Infections and Various Infective Conditions of the Eye
68.2.2 Viral Infections (Box 68.2)
Box 68.2 Antivirals Used in Viral Infective Conditions of the Eye
68.2.3 Fungal Infections (Box 68.3)
Box 68.3 Antifungals Used in Fungal Infective Conditions of the Eye
68.2.4 Protozoal Infections
68.3 Drugs Used in Glaucoma
68.4 Anti-Inflammatory and Immunomodulatory Drugs (Table 68.2)
68.5 Antihistamines and Mast Cell Stabilizers Used in Allergic Conditions
68.6 Ocular Toxicity of Systemic Agents (Table 68.3)
Bibliography
69: Nutritional Supplements and Herbal Medicines
69.1 Introduction
69.1.1 Differences from Pharmacotherapy
69.2 Regulations
69.2.1 FSSAI Regulations
69.2.2 Important Take-Away from the Guidelines
69.2.3 Manufacturing Regulations
69.3 Usage
69.4 Concerns Over Nutraceuticals
Bibliography
70: Immunoglobulins and Vaccines
70.1 Immunity
70.2 Vaccines and Types
70.2.1 Live Attenuated Vaccines (LAVs)
70.2.2 Toxoid
70.2.3 Killed/Inactivated Vaccine
70.2.4 Subunit Vaccine
70.3 Immunization Programme in India
70.4 Immunization in Pregnancy
Box 70.1 Inactivated and Live Attenuated Vaccines Approved to be Used in Pregnancy
Box 70.2 Vaccine Recommendations in Pregnancy
70.4.1 Tetanus Toxoid Vaccines
70.4.2 Inactivated Influenza Vaccine
70.4.3 Meningococcal Vaccine
70.4.4 Rubella Mono Vaccines and Combined Vaccines
70.4.5 Human Papilloma Virus (HPV) Vaccine
70.4.6 Yellow Fever Vaccine
70.5 Immunization for Travellers
70.6 Vaccines for Chronic Non-Communicable Diseases
70.6.1 Cancer Vaccines
70.6.2 Vaccines for Atherosclerosis
Box 70.3 Summary of Different Vaccine Targets
Bibliography